This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 1) Synthesis of novel nAChR (nicotinic acetylcholine receptor) ligands using the natural products nicotine, cytisine, and the precursor and metabolite of acetylcholine, choline, as templates. 2) Structure-affinity relationships studies for different nAChR subtypes (e.g. [unreadable]4/[unreadable]2*, [unreadable]3/[unreadable]4*, [unreadable]7*, muscle type) for the compounds synthesized using radioligand binding assays (competition studies). Further functional studies and in vivo experiments will be performed for selected compounds by the mentors/collaborators. 3) All data collected will be used to define the structural prerequisites important for an extended pharmacophore model in the future related to desirable affinities and functionalities for potential new smoking cessation drugs and antidepressant therapeutics. The aims have not been modified.